HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots.

Document Type

Article

Publication Date

3-2020

Keywords

JMG, JAXCC

JAX Source

Genes Dev 2020 Mar; 34(5-6):398-412

Volume

34

Issue

5-6

First Page

398

Last Page

412

ISSN

1549-5477

PMID

32001511

DOI

https://doi.org/10.1101/gad.333542.119

Grant

GM099640,GM133724,CA034196

Abstract

Chromatin barriers prevent spurious interactions between regulatory elements and DNA-binding proteins. One such barrier, whose mechanism for overcoming is poorly understood, is access to recombination hot spots during meiosis. Here we show that the chromatin remodeler HELLS and DNA-binding protein PRDM9 function together to open chromatin at hot spots and provide access for the DNA double-strand break (DSB) machinery. Recombination hot spots are decorated by a unique combination of histone modifications not found at other regulatory elements. HELLS is recruited to hot spots by PRDM9 and is necessary for both histone modifications and DNA accessibility at hot spots. In male mice lacking HELLS, DSBs are retargeted to other sites of open chromatin, leading to germ cell death and sterility. Together, these data provide a model for hot spot activation in which HELLS and PRDM9 form a pioneer complex to create a unique epigenomic environment of open chromatin, permitting correct placement and repair of DSBs.

Comments

We thank all members of the Baker laboratory for comments and discussion. We thank Petko Petkov and Anita Hawkins for Prdm9ΔZnf mice, as well as Tanmoy Bhattacharyya and Travis Kent for technical help with PRDM9 histological staining and staging seminiferous tubules. We thank Mary Ann Handel and Taneli Helenius for critical reading of the manuscript and suggestions. This work was assisted by The Jackson Laboratory Scientific Services.

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